Requirement for IGF-I in Epidermal Growth Factor-Mediated Cell Cycle Progression of Mammary Epithelial Cells

Induction of cyclin proteins is required for progression of cells through the G1-S and G2-M cell cycle checkpoints and is a primary mechanism by which mitogens regulate cell cycle progression. IGF-I and the epidermal growth factor (EGF)-related ligands are mitogens for mammary epithelial cells in vi...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2002-05, Vol.143 (5), p.1872-1879
Main Authors: Stull, Malinda A, Richert, Monica M, Loladze, Aimee V, Wood, Teresa L
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cell cycle
Cell Cycle - physiology
Cell Division - physiology
Cyclin G
Cyclin G1
Cyclin G2
Cyclins
Cyclins - biosynthesis
Cyclins - genetics
DNA - biosynthesis
DNA - genetics
DNA Replication - physiology
Epidermal growth factor
Epidermal Growth Factor - physiology
Epithelial cells
Epithelial Cells - physiology
Epithelium
Female
Gene expression
Gene Expression Regulation
Growth factors
Immunohistochemistry
Insulin-like growth factor I
Insulin-Like Growth Factor I - physiology
Ligands
Mammary gland
Mammary glands
Mammary Glands, Animal - cytology
Mammary Glands, Animal - physiology
Mice
Mitogens
Nuclease Protection Assays
Organ Culture Techniques
Transforming growth factor-a
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Summary:Induction of cyclin proteins is required for progression of cells through the G1-S and G2-M cell cycle checkpoints and is a primary mechanism by which mitogens regulate cell cycle progression. IGF-I and the epidermal growth factor (EGF)-related ligands are mitogens for mammary epithelial cells in vitro and are essential for growth of the mammary epithelium during development. We report here that IGF-I in combination with EGF or TGFα is synergistic in promoting DNA synthesis in mammary epithelial cells in the intact mammary gland cultured in vitro. We further investigated the role of IGF-I and EGF in cyclin expression and cell cycle progression in the mammary gland and demonstrate that IGF-I and EGF induce expression of early G1 cyclins. However, we show that IGF-I, but not EGF, induces late G1 and G2 cyclins and is required for mammary epithelial cells to overcome the G1-S checkpoint. These data demonstrate that IGF-I is essential for cell cycle progression in mammary epithelial cells and that it is required for EGF-mediated progression past the G1-S checkpoint in these cells.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.143.5.8774